脂代谢异常（脂肪酸及脂滴代谢）与细胞自噬在肿瘤发生发展中起重要作用，且两者互相调控。我们前期研究发现破壁灵芝孢子粉多糖(GLP)显著抑制结肠癌细胞HCT116的增殖, 并诱导细胞凋亡。然而,GLP是否调控脂代谢重编程及自噬来抑制癌细胞增殖的研究在国内外尚未见诸报导。我们最新研究发现GLP显著增加结肠癌细胞内脂滴积累;并诱导MAPK/ERK介导的Beclin-1非依赖性自噬小体积聚及阻断自噬流发生，从而诱导细胞凋亡。在此基础上,本课题拟在体内及体外采用各种分子生物学手段基于MAPK/ERK信号通路研究GLP调控结肠癌细胞HCT116 与HT-29中脂肪酸代谢重编程(包括脂肪酸运转与摄取、合成、分解等)、能量代谢、脂滴积累及其与细胞自噬相互调控的作用，及抑制Beclin-1的作用等来深入研究GLP抗结肠癌的作用机制。本课题的完成将为从调控脂代谢及自噬中找到GLP抗肿瘤的新靶点。

Abnormal lipid metabolism （fatty acid and lipid droplet）and autophagy play important regulatory roles in tumor development, and they regulate each other. Our previous study found that the powder of broken spores of Ganoderma lucidum (G. lucidum) polysaccharide (GLP) significantly inhibited the proliferation of colorectal cancer HCT116 cells and induced apoptosis. However, whether GLP can inhibit the proliferation of cancer cells by regulating lipid metabolism reprogramming and autophagy has not been reported. We recently found that GLP significantly induced lipid droplet accumulation, and induced MAPK/ERK-mediated Beclin-1 independent autophagosome accumulation, blocked autophagic flux in colorectal cancer cells. These effects are responsible for GLP-induced apoptosis. Based on the current study, we proposed to study both in vivo and in vitro using various molecular biology methods to study effects of GLP on regulating fatty acids metabolic reprogramming (including fatty acid intake, synthesis and decomposition, transportation, etc.), energy metabolism, lipid droplets accumulation and its interaction with autophagy, and Beclcin-1 regulation in colorectal cancer HCT116 and HT-29 cells. Our study is aimed to further study the molecular mechanisms of GLP against colorectal cancer. The completion of this project will find a new anti-tumor mechanism of GLP through targeting lipid metabolism and autophagy.